In-silico Study of Secondary Metabolites as Potential Inhibitors of NEF and P24 Protein of HIV-1

Abstract

Introduction: Acquired immune deficiency syndrome (HIV/AIDS) has been a major global health concern for over 38 years. No safe and effective preventive or therapeutic vaccine has been developed although many products have been investigated. Methods: This computational study was conducted on plant-based active compounds against HIV-1 NEF and p24 protein to obtain and complexes with high binding scores were used for two-dimensional interaction studies via Ligplot to explore hydrogen bond and hydrophobic bond formation. ADMET analysis for best phytocompounds was performed using DruLito, ALOGPS, and PROTOX II. Results: According to the study conducted, phytocompounds like, Protostrychnine, Isostrychnine, Pseudo-Alpha-Colubrine, Alpha-Colubrine, Camptothecin, Benzo[f]quinoline, and (+) -Camptothecin are safe to be considered as a potential drug candidate after experimental validation against NEF and p24 proteins of HIV-1. While, Picrasidine M, Chaetochromin, 3’,3’-Binaringenin, and Sequoiaflavone displayed high binding scores of -10.8, -8.2, -9.5, -9.2 and -9.0, -8.8, -10.6, -9.0 respectively for NEF and p24 protein. All drugs belong to the toxicity class of either 4 or 5. They are inactive for hepatotoxicity and carcinogenicity but active for immunogenicity. Conclusion: For further validation of the results the phytocompounds can be extracted through solvent extraction method and tested on cell lines or animal models for their effectiveness.